Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN

Merlotti, Antonela; Dantas, Ezequiel; Lenicov, Federico Remes; Ceballos, Ana; Jancic, Carolina; Varese, Augusto; Rubione, Julia; Stover, Sofia; Geffner, Jorge; Sabatté, Juan

doi:10.1093/humrep/dev113

Cited by 27 publications

(26 citation statements)

References 52 publications

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“…The fact that serum CLU does not demonstrate such features is interesting. Merlotti et al (2015) proved that seminal plasma CLU plays an important role in the utilization of damaged proteins. CLU inhibits aggregation of the destroyed proteins and forwards them to the DCs through DC‐SIGN.…”

Section: The Role Of Clu Glycosylationmentioning

confidence: 99%

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Could the glycosylation analysis of seminal plasma clusterin become a novel male infertility biomarker?

Janiszewska¹,

Kratz²

2020

Molecular Reproduction Devel

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Male infertility is becoming a rapidly growing problem around the world, mainly in the highly developed countries. Seminal proteome composition seems to be one of the crucial factors of the proper course of fertilizationclusterin (CLU) is among the most important ones. CLU, as one of the crucial seminal plasma glycoproteins, plays a very important role in sperm capacitation and immune tolerance in the female reproductive tract. CLU is also known as a sensitive marker of oxidative stress. It has six N-glycosylation sites and also exhibits chaperone activity. An analysis of changes in the profile and degree of CLU glycosylation may shed some new light on the molecular mechanisms of the fertilization process and may be used as an additional diagnostic marker of male fertility. This study constitutes a review of the recently available literature concerning human seminal CLU, including changes in its glycosylation, analyzed in the context of human reproduction. K E Y W O R D S clusterin, male fertility, semen quality, seminal clusterin glycosylation

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Section: The Role Of Clu Glycosylationmentioning

confidence: 99%

“…The interactions between DCs and CLU result in DCs stimulation. Merlotti et al (2015) presumed that it might be essential in the induction of immune tolerance in the female reproductive tract.…”

Section: The Role Of Clu Glycosylationmentioning

confidence: 99%

Could the glycosylation analysis of seminal plasma clusterin become a novel male infertility biomarker?

Janiszewska¹,

Kratz²

2020

Molecular Reproduction Devel

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“…29 Semen mediates the expansion of Tregs in DLN of the genital tract and their subsequent recruitment to the uterine endometrium. 1,13 This tolerogenic response is induced even in the absence of conception, suggesting a major role for SP in eliciting this effect. 11 Moreover, it was shown to be completely dependent on the presence of SVF, as mating with seminal vesicle-deficient males failed to induce the expansion of Tregs.…”

Section: Discussionmentioning

confidence: 92%

“…12 Moreover, we also showed that a protein found at high concentrations in the SP, clusterin, promotes the expansion of Tregs by DCs. 13 A very important question that remains to be answered is whether deposition of SP in the female reproductive tract might also be capable of suppressing the adaptive immune response against pathogens in a similar way to the immune response against paternal antigens. As semen is the main vector for sexually transmitted infectious diseases that annually causes millions of deaths in the world, 14 it is striking that the ability of semen to modulate the course of the anti-microbial immune response has not been analyzed.…”

Section: Introductionmentioning

confidence: 99%

Seminal vesicle fluid increases the efficacy of intravaginal HSV-2 vaccination

et al. 2018

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Once considered merely as a vehicle for spermatozoa, it is now clear that seminal plasma (SP) induces a variety of biological actions on the female reproductive tissues able to modulate the immune response against paternal antigens. To our knowledge, the influence of SP on the immune response against sexually transmitted pathogens has not been yet evaluated. We here analyzed whether the seminal vesicle fluid (SVF), which contributes almost 60% of the SP volume in mice, could modulate the immune response against herpes simplex virus type 2 (HSV-2). We found that SVF does not modify the course of primary infection, but markedly improved protection conferred by vaginal vaccination with inactivated HSV-2 against a lethal challenge. This protective effect was shown to be associated to a robust memory immune response mediated by CD4+ and CD8+ T cells in both the lymph nodes draining the vagina and the vaginal mucosa, the site of viral replication. In contrast with the widespread notion that SP acts as an immunosuppressive agent, our results suggest that SVF might improve the female immune response against sexually transmitted pathogens.

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“…CLU present in the rete testis fluid is synthesized by Sertoli cells and adheres to the surface of testicular spermatozoa. When spermatozoa move through the rete testis and efferent duct, testis-derived CLU is replaced by CLU from the epididymal or seminal vesicle (Griffiths et al, 2009).CLU expression is negatively associated with the percentage of normal sperm morphology (Santos et al, 2014) and high expression of CLU promotes the uptake of stress-damaged proteins by dendritic cells in male reproductive tract (Merlotti et al, 2015).…”

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confidence: 99%

Relationship between Clusterin Gene Expression and In-vitro Sperm Characteristics in Caprine Semen

Vengatachalam¹

2019

JAR

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The present experiment was undertaken to study the relationship between clusterin (CLU) gene expression and in vitro sperm characteristics in buck semen. Fresh semen samples were collected from 12 bucks maintained in the organized goat farms by artificial vagina. Normalization of initial concentration of spermatozoa was carried out in all buck semen samples before proceeding for RNA isolation. So, initial concentration of each sample was made equal. The spermatozoa were isolated from buck semen samples by swim-up protocol using sperm TALP. Total RNA from the buck spermatozoa were extracted and first strand cDNA was synthesized from 1μg total RNA by using commercial kits. Absolute quantification of CLU gene transcripts in semen samples from 12 bulls was performed by plotting standard curve. Variations in levels of CLU gene transcripts (2500-22546000 copies) were found among 12 different buck semen samples. In vitro sperm characteristics were also studied from 12 buck semen samples. Variations in sperm characteristics such as sperm motility (60.0-80.0%), sperm viability (72.0-93.0%), sperm morphology (73.0-91.0%), plasma membrane integrity (50.0-82.0%), acrosome integrity (81.0-93.0%), DNA integrity (82.0-93.0%) and MMP (46.0-74.0%) were found among buck semen samples. All in vitro sperm characteristics were highly (negatively) correlated (p<0.01) with expression levels of CLU gene transcripts in spermatozoa. From this study, it is evident that ejaculated buck semen has variations in transcription pattern of CLU gene in spermatozoa among bucks and expression levels of CLU transcripts have negative correlation with in vitro sperm characteristics in buck semen samples.

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Fucosylated clusterin in semen promotes the uptake of stress-damaged proteins by dendritic cells via DC-SIGN

Abstract: The present research was supported by the Consejo Nacional de Investigaciones Científicas y Técnicas, the Buenos Aires University School of Medicine, and the Agencia Nacional de Promoción Científica y Tecnológica (Argentina). The authors have no conflicts of interest to declare.

Cited by 27 publications

References 52 publications

Could the glycosylation analysis of seminal plasma clusterin become a novel male infertility biomarker?

Could the glycosylation analysis of seminal plasma clusterin become a novel male infertility biomarker?

Seminal vesicle fluid increases the efficacy of intravaginal HSV-2 vaccination

Relationship between Clusterin Gene Expression and In-vitro Sperm Characteristics in Caprine Semen

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